DESCRIPTION: Several lines of evidence suggest that the nervous system contributes importantly to the development of NaCl-sensitive hypertension. Our previous studies demonstrate that in NaCl- sensitive spontaneously hypertensive rats (SHR-S), excessive dietary NaCl leads to a significant decrease in noradrenaline (NA) release in the anterior hypothalamic area (AHA). This in turn reduces sympathetic nervous system inhibition, resulting in a rise in arterial pressure. Our previous studies suggest that the reduction of NA release in the AHA of SHR-S on a high NaCl diet decreases the activity of AHA neurons. In the first specific aim, we will test the hypothesis that in NaCl-resistant rats (e.g. WKY), exposure to a high NaCl diet causes AHA neurons to increase activity, thus restraining sympathetic nervous system activity. In contrast, we hypothesize that in SHR-S, exposure to a high NaCl diet will cause much less (if any) increase in neuronal activity in the AHA, resulting in a rise in arterial pressure due to the lack of sympathetic nervous system restraint. This will be tested by quantifying the AHA content and expression of the immediate early genes and their protein products. Recently we have found that in SHR-S, dietary NaCl supplementation causes a nearly immediate and rapidly increasing elevation of nighttime arterial pressure but induces a much more slowly developing increase in daytime arterial pressure. Thus, in SHR-S during the nighttime (when the sympathetic nervous system is highly active), arterial pressure displays an almost immediate hypertensive response to a high NaCl diet, but during the daytime (when sympathetic nervous system activity is greatly reduced), arterial pressure increases much more slowly (over weeks). While previous studies of NaCl- sensitivity (which were nearly all conducted during the daytime) have elucidated the neuronal mechanism(s) underlying the hypertensive response that develops over a two week feeding period, the mechanisms that underlie the very rapid nighttime response have not been studied, but they likely contribute importantly to the longer term changes. Studies in the first specific aim will test the day/night changes in the activity of AHA neurons in SHR-S and WKY on high and basal NaCl diets. The second specific aim will test the hypothesis that the sympathetic nervous system overactivity that leads to NaCl-sensitive hypertension in the SHR-S has a circadian rhythm that relates to the diurnal suppression of NA release in the AHA. The mechanism by which excess dietary NaCl effects NA release in the AHA has remained enigmatic; however, our recent experiments demonstrate that a high NaCl diet results in a rapid, transient elevation (approximately 4 mEq) of plasma Na+. An 20 minute, intravenous infusion of NaCl that elevates plasma Na+ by 4 mEq causes a longlasting decrease in NA release in AHA of SHR-S. The third specific aim will test the hypothesis that the response to such elevations in plasma Na+ are responded to differently by SHR-S and WKY and that this differential response underlies NaCl- sensitive hypertension in SHR-S.